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| 001 | 291769 | ||
| 005 | 20250213095848.0 | ||
| 024 | 7 | _ | |a 10.1038/s41380-024-02670-x |2 doi |
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| 100 | 1 | _ | |a Stocker, Hannah |0 P:(DE-He78)104fae0755c89365b7ae32238b3f1f52 |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Mitochondrial DNA abundance in blood is associated with Alzheimer's disease- and dementia-risk. |
| 260 | _ | _ | |a London |c 2025 |b Macmillan |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 500 | _ | _ | |a #EA:C070#LA:C070# / 30, pages 131–139 (2025) |
| 520 | _ | _ | |a The mitochondrial cascade hypothesis of Alzheimer's disease (AD) has been portrayed through molecular, cellular, and animal studies; however large epidemiological studies are lacking. This study aimed to explore the association of mitochondrial DNA copy number (mtDNAcn), a marker representative of mtDNA abundance per cell, with risk of incident all-cause dementia, AD, and vascular dementia diagnosis within 17 years and dementia-related blood biomarkers (P-tau181, GFAP, and NfL). Additionally, sex-stratified analyses were completed. In this German population-based cohort study (ESTHER), 9940 participants aged 50-75 years were enrolled by general practitioners and followed for 17 years. Participants were included in this study if information on dementia status and blood-based mtDNAcn measured via real-time polymerase chain reaction were available. In a nested case-control approach, a subsample of participants additionally had measurements of P-tau181, GFAP, and NfL in blood samples taken at baseline. Of 4913 participants eligible for analyses, 386 were diagnosed with incident all-cause dementia, including 130 AD and 143 vascular dementia cases, while 4527 participants remained without dementia diagnosis within 17 years. Participants with low mtDNAcn (lowest 10%) experienced 45% and 65% percent increased risk of incident all-cause dementia and AD after adjusting for age and sex (all-cause dementia: HRadj, 95%CI:1.45, 1.08-1.94; AD: HRadj, 95%CI: 1.65, 1.01-2.68). MtDNAcn was not associated to vascular dementia diagnosis and was more strongly associated with all-cause dementia among women. In the nested case-control study (n = 790), mtDNAcn was not significantly associated with the dementia-related blood biomarkers (P-tau181, GFAP, and NfL) levels in blood from baseline before dementia diagnosis. This study provides novel epidemiological evidence connecting mtDNA abundance, measured via mtDNAcn, to incident dementia and AD at the population-based level. Reduced mitochondrial abundance may play a role in pathogenesis, especially among women. |
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| 700 | 1 | _ | |a Gentiluomo, Manuel |b 1 |
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| 700 | 1 | _ | |a Beyer, Léon |b 3 |
| 700 | 1 | _ | |a Stevenson-Hoare, Joshua |0 P:(DE-He78)9976da2c4ac21202b44584c21d8404e7 |b 4 |u dkfz |
| 700 | 1 | _ | |a Rujescu, Dan |0 0000-0002-1432-313X |b 5 |
| 700 | 1 | _ | |a Holleczek, Bernd |b 6 |
| 700 | 1 | _ | |a Beyreuther, Konrad |b 7 |
| 700 | 1 | _ | |a Gerwert, Klaus |b 8 |
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| 700 | 1 | _ | |a Campa, Daniele |b 10 |
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| 700 | 1 | _ | |a Brenner, Hermann |0 P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2 |b 12 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1038/s41380-024-02670-x |0 PERI:(DE-600)1502531-7 |p 131–139 |t Molecular psychiatry |v 30 |y 2025 |x 1359-4184 |
| 856 | 4 | _ | |u https://inrepo02.dkfz.de/record/291769/files/s41380-024-02670-x.pdf |
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